The Harry M. Zweig Memorial Fund for Equine Research

Influence of an Underlying Immune Environment on the Subsequent IgG Isotype Response to a Foreign Antigen

Dr. Dorothy M. Ainsworth

The
primary objective of this project will be to investigate how an underlying
inflammatory condition, like heaves (also known as recurrent airway
obstruction (RAO) or chronic obstructive pulmonary disease, COPD), affects
or biases the immune system. We will specifically examine whether a
symptomatic heavey horse can develop an antibody response to a nebulized
vaccine to the same degree as either a control healthy horse or an asymptomatic
horse prone to heaves. Once we have quantitated the antibody response
in the horses' lungs and blood, we will determine if the strength of
the humoral response is correlated with the magnitude of the immune
mediator (cytokine) response of the immune cells in these two compartments.

We study the immune responses in heavey horses for several
reasons: This medical condition is one of the most common disorders
seen in horses referred to the Cornell University Hospital for
Animals. Heaves is found in middle-aged and older horses and
is precipitated by exposure to hay and bedding materials. The
condition, which resembles asthma in humans, is characterized
by neutrophil accumulation in the small bronchioles, bronchospasm
and mucus accumulation. It severely limits the athletic usefulness
of these horses contributing to owner frustration and horse wastage.

Secondly, we study heaves because it is unknown if conventional
vaccines, administered either intramuscularly or intranasally,
might adversely affect the airway obstruction, or thirdly, whether
the inflammatory condition of heaves might prevent an adequate
immune response from developing.

The importance of determining whether an immunological bias
is conferred from an underlying condition like heaves to subsequent
antigen encounters has implications that extend beyond the study
of heavey horses. For example, consider the case of a young foal
infected with intestinal roundworms. As part of their life cycle,
these parasites migrate through the foal's lungs, establishing
a chronic inflammatory response characterized as a T helper cell
2 reaction. The ensuing T helper cell 2 environment, with production
of certain immune mediators or cytokines, might deter the ability
of the pulmonary and systemic immune cells to produce antibodies
against either inhaled bacteria and viruses or to normally-administered
vaccines. Such a phenomenon has been documented in mice, rats
and guinea pigs, but not in the horse. The net result is that
the Th-2 environment negatively impacts on the pulmonary and
systemic health of the foal.

Understanding what conditions are optimal for the development of an immune
response—what conditions enhance or diminish antibody production—is
critical for improvements in equine health and in equine vaccine development.